This revised biomedical partnership proposal from the Univ. of Chicago and Argonne National Lab aims to develop an intra-arrest cooling system for field use by paramedics during cardiac arrest and is directly responsive to the NIH PULSE Workshop calling for new resuscitation methods. Two prototype microparticle slurries have been developed: one saline-based for intravascular use and another perfluorocarbon-based for pulmonary use. These slurries contain high percentages of small (100mum) highly fluid, smooth ice particles with 8 times the cooling capacity of the same liquid (0 degrees C) without ice. In initial swine studies saline slurry resulted in very rapid brain and heart cooling (>1 degree C every 2 minutes) during cardiac arrest with only chest compression to produce circulation, far superior to any external cooling techniques. Moreover, adverse effects of 30 minutes exposure to perfluorocarbon slurry instilled into the lungs of normal animals (not in cardiac arrest) were mild and improved with time. Animals survived unassisted for 48 hours with A-a gradients not significantly different from controls. Thus, creating an optimal cooling method with minimal adverse effects appears a realistic goal. Specific aims and milestones include: (i) bioengineering and developing two microparticulate slurries for pulmonary and intravenous use, (ii) using these slurries to optimize "intra-arrest" cooling rates of the heart and brain of animals during cardiac arrest, (iii) describing and minimizing adverse effects of slurries, and finally (iv) testing whether slurry cooling to 2 different levels of intra-arrest low-flow cooling will improve survival in a swine model of cardiac arrest. Unlike any existing method, paramedics could use this cooling method after failed defibrillation in efforts to delay additional heart and brain damage until full reperfusion can occur. An international advisory committee of noted resuscitation experts will advise the project and many wish to test the slurries in their home laboratories after completion of these aims, increasing the potential impact of this work.